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. 2025 Jul 30:18:10283-10293.
doi: 10.2147/JIR.S507083. eCollection 2025.

The Different Immune Response Between Onset and Remission of AQP4 Antibody-Positive Optic Neuritis Based on RNA Sequencing of Whole Blood

Ruohan Shi #  1 , Yidan Luo #  2   3 , Yusheng Chen #  1   2 , Xuelian Chen  4 , Shiyi Li  5 , Ziqing Chen  1 , Ke Wang  6   7 , Wenjun Zou  1   2
Affiliations

The Different Immune Response Between Onset and Remission of AQP4 Antibody-Positive Optic Neuritis Based on RNA Sequencing of Whole Blood

Ruohan Shi et al. J Inflamm Res. .

Abstract

Purpose: We aimed to investigate differences in the immune response between the onset and remission phases of AQP4 antibody-positive optic neuritis (AQP4-ON).

Methods: Whole blood samples were collected from 7 healthy volunteers, 6 patients with AQP4-ON in the acute phase and 6 patients with AQP4-ON in the remission phase. Gene expression patterns and immune response pathways associated with the disease phases were identified by sequencing the RNA. CIBERSORTx was used to identify infiltrated immune cells.

Results: The enrichment analysis showed that Toll-like receptors, cytokine activity and neutrophil-mediated immune activity were significantly enriched in the acute phase, whereas cell cycle pathway was significantly enriched in the remission phase. TSPO and CDK1 were the core genes in the acute and remission phases, respectively. TSPO expression was positively correlated with M0 macrophages and neutrophils, whereas it was significantly negatively correlated with CD8 T cells (rs=0.66, P=0.0195) and resting natural killer (NK) cells (rs=0.6662, P=0.0180). Best corrected visual acuity (BCVA; logMAR) was positively correlated with activated CD4 memory T cells and resting NK cells and negatively correlated with neutrophils in the acute phase. BCVA (LogMAR) was negatively correlated with monocytes, CD8 T cells, and M0 macrophages and positively correlated with neutrophils in the remission phase.

Conclusion: The present findings provide valuable insights into different immune responses during different phases of AQP4-ON, which is helpful for patients to develop targeted therapies and personalized treatment strategies.

Keywords: AQP4 antibody-positive optic neuritis; RNA sequencing; gene expression; immune response; inflammation.

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Conflict of interest statement

The author(s) report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Functional enrichment analysis of acute stage (A) group, remission stage (R) group and healthy control (HC) group. (A) PCA analysis of three groups. (B) Venn diagram of three groups. (C) Heat map of three groups.
Figure 2
Figure 2
Differential gene expression analysis. (A) Volcano diagram of the differential expression gene in A group and HC group. (B) Volcano diagram of the differential expression gene in R group and HC group. (C) GO term enrichment analysis in A group and HC group. (D) GO term enrichment analysis in R group and HC group. (E) KEGG enrichment analysis in A group and HC group. (F) KEGG enrichment analysis in R group and HC group.
Figure 3
Figure 3
PPI network analysis of different genes. (A) PPI network analysis of different genes in A group and HC group. (B) PPI network analysis of different genes in R group and HC group.
Figure 4
Figure 4
Analysis of immune cell infiltration. (A) PCA analysis of infiltrating immune cells. (B) Cumulative histogram of the proportion of 22 infiltrating immune cells in each sample, and the total proportion of the 22 infiltrating immune cells is equal to 100%. (C) Heat map of 22 infiltrating immune cells in each sample.
Figure 5
Figure 5
Correlation analysis. (A) Spearman correlation analysis between infiltrating immune cell proportion and BCVA at last follow-up in A group. (B) Spearman correlation analysis between infiltrating immune cell proportion and BCVA at last follow-up in R group. (C) Spearman correlation analysis between infiltrating immune cell proportion and TSPO gene expression in AQP4-ON.
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